Chemically crosslinked ultrahigh molecular weight polyethylene for artificial human joints

ABSTRACT

The present invention discloses a method for enhancing the wear-resistance of polymers by crosslinking them, especially before irradiation sterilization. In particular, this invention presents the use of chemically crosslinked ultrahigh molecular weight polyethylene in in vivo implants.

TECHNICAL FIELD OF THE INVENTION

[0001] The present invention relates to polymers. It discloses a methodfor enhancing the wear-resistance of polymers, especially polymers thatare to be irradiated, by crosslinking the polymers. The crosslinkedpolymers may be annealed to stabilize their size shrinkage. The polymersdisclosed herein are particularly useful for making in vivo implants.

BACKGROUND OF THE INVENTION

[0002] Ultrahigh molecular weight polyethylene (hereinafter referred toas “UHMW polyethylene”) is commonly used to make prosthetic joints suchas artificial hip joints. In recent years, it has become increasinglyapparent that tissue necrosis and interface osteolysis, in response toUHMW polyethylene wear debris, are primary contributors to the long-termloosening failure of prosthetic joints. For example, the process of wearof acetabular cups of UHMW polyethylene in artificial hip jointsintroduces many microscopic wear particles into the surrounding tissues.The reaction of the body to these particles includes inflammation anddeterioration of the tissues, particularly the bone to which theprosthesis is anchored. Eventually, the prosthesis becomes painfullyloose and must be revised. It is generally accepted by orthopaedicsurgeons and biomaterials scientists that the reaction of tissue to weardebris is the chief cause of long-term failure of such prostheses.

[0003] Laboratory experiments and examination of worn polyethylenecomponents, as used in acetabular cups of total hip prostheses, afterremoval from patients, have shown that polyethylene wear in vivoprimarily involves three fundamental mechanisms: adhesive, abrasive, andfatigue wear (Brown, K. J., et al., Plastics in Medicine & SurgeryPlastics & Rubber Institute, London, 2.1-2.5 (1975); Nusbaum, H. J. &Rose, R. M., J. Biomed. Materials Res., 13:557-576 (1979); Rostoker, W.,et al., J. Biomed. Materials Res., 12:317-335 (1978); Swanson, S. A. V.& Freeman, M. A. R., Chapter 3, “Friction, lubrication and wear.”, TheScientific Basis of Joint Replacement, Pittman Medical Publishing Co.,Ltd. (1977).)

[0004] Adhesive wear occurs when there is local bonding betweenasperities on the polymer and the opposing (metal or ceramic)counterface. If the ratio of the strength of the adhesive bond to thecohesive strength of the polymer is great enough, the polymer may bepulled into a fibril, finally breaking loose to form a wear particle.Small wear particles (measuring microns or less) are typically produced.

[0005] Abrasive wear occurs when asperities on the surface of thefemoral ball, or entrapped third-body particles, penetrate into thesofter polyethylene and cut or plow along the surface during sliding.Debris may be immediately formed by a cutting process, or material maybe pushed to the side of the track by plastic deformation, but remain anintegral part of the surface.

[0006] Fatigue wear is dependent on cyclic stresses applied to thepolymer. As used herein, fatigue wear is an independent wear mechanisminvolving crack formation and propagation within the polymer. Cracks mayform at the surface and coalesce, releasing wear particles as large asseveral millimeters and leaving behind a corresponding pit on thesurface, or cracks may form a distance below the surface and travelparallel to it, eventually causing sloughing off of large parts of thesurface.

[0007] There are gaps in the prior art regarding the contributions ofthe above three basic mechanisms to the wear of polyethylene cups invivo. While numerous laboratory studies and analyses of retrievedimplants have provided valuable details on wear in vivo, there isongoing disagreement regarding which wear mechanisms predominate andwhat are the controlling factors for wear.

[0008] However, it is clear that improving the wear resistance of theUHMW polyethylene socket and, thereby, reducing the amount of weardebris generated each year, would extend the useful life of artificialjoints and permit them to be used successfully in younger patients.Consequently, numerous modifications in physical properties of UHMWpolyethylene have been proposed to improve its wear resistance.

[0009] UHMW polyethylene components are known to undergo a spontaneous,post-fabrication increase in crystallinity and changes in other physicalproperties. (Grood, E. S., et al., J. Biomedical Materials Res.,16:399-405 (1976); Kurth, J., et al., Trans. Third World BiomaterialsCongress, 589 (1988); Rimnac, C. M., et al., J. Bone & Joint Surgery,76-A(7):1052-1056 (1994)). These occur even in stored (non-implanted)cups after sterilization with gamma radiation which initiates an ongoingprocess of chain scission, crosslinking, and oxidation or peroxidationinvolving free radical formation. (Eyerer, P. & Ke, Y. C., J. Biomed.Materials Res. 18:1137-1151 (1984); Nusbaum, H. J. & Rose, R. M., J.Biomed. Materials Res., 13:557-576 (1979); Roe, R. J., et al., J.Biomed. Materials Res., 15:209-230 (1981); Shen, C. & Dumbleton, J. H.,Wear, 30:349-364 (1974)). These degradative changes may be acceleratedby oxidative attack from the joint fluid and cyclic stresses appliedduring use. (Eyerer, P. & Ke, Y. C., J. Biomed. Materials Res., supra;Grood, E. S., et al., J. Biomed. Materials Res., supra; Rimnac, C. M.,et al., ASTM Symposium on Biomaterials' Mechanical Properties,Pittsburgh, May 5-6 (1992)).

[0010] On the other hand, it has been reported that the best total hipprosthesis for withstanding wear is one with an alumina head and anirradiated UHMW polyethylene socket, as compared to a un-irradiatedsocket. The irradiated socket had been irradiated with 10⁸ rad ofγ-radiation, or about 40 times the usual sterilization dose. (Oonishi,H., et al., Radiat. Phys. Chem., 39(6):495-504 (1992)). The usualaverage sterilization dose ranges from 2.5 to 4.0 Mrad. Otherinvestigators did not find any significant reduction in the wear ratesof UHMW polyethylene acetabular cups which had been irradiated, in thesolid phase, in special atmospheres to reduce oxidation and encouragecrosslinking. (Ferris, B. D., J. Exp. Path., 71:367-373 (199b); Kurth,M., et al., Trans. Third World Biomaterials Congress, 589 (1988); Roe,R. J., et al., J. Biomed. Materials Res., 15:209-230 (1981); Rose, etal., J. Bone & Joint Surgery, 62A(4):537-549 (1980); Streicher, R. M.,Plastics & Rubber Processing & Applications, 10:221-229 (1988)).

[0011] Meanwhile, DePuy.DuPont Orthopaedic has fabricated acetabularcups from conventionally extruded bar stock that has previously beensubjected to heating and hydrostatic pressure that reduces fusiondefects and increases the crystallinity, density, stiffness, hardness,yield strength, and resistance to creep, oxidation and fatigue. (U.S.Pat. No. 5,037,928, to Li, et al.,l Aug. 6, 1991; Huang, D. D. & Li, S.,Trans. 38th Ann. Mtg., Orthop. Res. Soc., 17:403 (1992); Li, S. &Howard, E. G., Trans. 16th Ann. Society for Biomaterials Meeting,Charleston, S.C., 190 (1990).) Silane cross-linked UHMW polyethylene(XLP) has also been used to make acetabular cups for total hipreplacements in goats. In this case, the number of in vivo debrisparticles appeared to be greater for XLP than conventional UHMWpolyethylene cup implants (Ferris, B. D., J. Exp. Path., 71:367-373(1990)).

[0012] Other modifications of UHMW polyethylene have included: (a)reinforcement with carbon fibers (“Poly Two Carbon—PolyethyleneComposite—A Carbon Fiber Reinforced Molded Ultra-High Molecular WeightPolyethylene”, Technical Report, Zimmer (a Bristol-Myers SquibbCompany), Warsaw (1977)); and (b) post processing treatments such assolid phase compression molding (Eyerer, P., Polyethylene, ConciseEncyclopedia of Medical & Dental Implant Materials, Pergamon Press,Oxford, 271-280 (1990); Li, S., et al., Trans. 16th Annual Society forBiomaterials Meeting, Charleston, S.C., 190 (1990); Seedhom, B. B., etal., Wear, 24:35-51 (1973); Zachariades, A. E., Trans. Fourth WorldBiomaterials Congress, 623 (1992)). However, to date, none of thesemodifications has been demonstrated to provide a significant reductionin the wear rates of acetabular cups. Indeed, carbon fiber reinforcedpolyethylene and a heat-pressed polyethylene have shown relatively poorwear resistance when used as the tibial components of total kneeprosthesis. (Bartel, D. L., et al., J. Bone & Joint Surgery,68-A(7):1041-1051 (1986); Conelly, G. M., et al., J. Orthop. Res.,2:119-125 (1984); Wright, T. M., et al., J. Biomed. Materials Res., 15:719-730 (1981); Bloebaum, R. D., et al., Clin. Orthop., 269:120-127(1991); Goodman, S. & Lidgren, L., Acta Orthop. Scand., 63(3) 358-364(1992); Landy, M. M. & Walker, P. S., J. Arthroplasty, Supplement,3:S73-S85 (1988); Rimnac, C. M., et al., Trans. Orthopaedic ResearchSociety, 17:330 (1992); Rimnac, C. M. et al., “Chemical and mechanicaldegradation of UHMW polyethylene: Preliminary report of an in vitroinvestigation,” ASTM Symposium on Biomaterials' Mechanical Properties,Pittsburgh, May 5-6 (1992)).

SUMMARY OF THE INVENTION

[0013] One aspect of the invention presents a method for reducing thecrystallinity of a polymer so that it can better withstand wear. Aneffective method for reducing the crystallinity of the polymer is bycrosslinking. For reduction of crystallinity, the polymer may beirradiated in the melt or, preferably, chemically crosslinked in themolten state. The method is particularly useful for polymer whichundergoes irradiation sterilization in the solid state. It isadvantageous if the crosslinked polymer is annealed to stabilize itsshrinkage.

[0014] Another aspect of the invention presents a method for making invivo implants based on the above treatment of the polymer.

[0015] Another aspect of the invention presents a polymer, made from theabove method, having an increased ability to withstand wear.

[0016] Another aspect of the invention presents in vivid implants madefrom the polymer described above.

BRIEF DESCRIPTION OF THE DRAWINGS

[0017]FIG. 1 presents SEM micrographs of fracture surfaces of thecompression molded UHMW polyethylene (after irradiation) atmagnifications of (A)×200 and (B)×5000.

[0018]FIG. 2 presents SEM micrographs of fracture surfaces ofcompression molded UHMW polyethylene crosslinked with 1 wt % peroxide(after irradiation) at magnifications of (A)×200 and (B)×5000.

[0019]FIG. 3 presents the geometry of the acetabular cup tested for wearon the hip joint simulator used in EXAMPLE 2 below,.

[0020]FIG. 4 presents a schematic diagram of the hip joint simulatorused in EXAMPLE 2 below.

[0021]FIG. 5 presents a graph comparing the amounts of wear of themodified and unmodified UHMW polyethylene cups during a run lasting amillion cycles.

DETAILED DESCRIPTION OF THE INVENTION

[0022] Abbreviations used in this application are as follows:

[0023] DSC—differential scanning calorimetry.

[0024] FTIR—Fourier Transform Infrared Spectroscopy

[0025] SEM—scanning electron microscopy

[0026] UHMW—ultra-high molecular weight

[0027] UHMWPE—ultra-high molecular weight polyethylene, also referred toas UHMW polyethylene

[0028] WAXS—wide angle X-ray scattering

[0029] Cutting through the plethora of choices and confusion in the art,applicants discovered that a low degree of crystallinity is a majorfactor in increasing the ability of polyethylene to withstand wear invivo, contrary to the above teaching of DePuy.DuPont Orthopaedic. Solidpolymers that can crystallize generally contain both crystalline andamorphous states. These two states have different physical properties.The applicants believe that the crystalline component of polymers ismore brittle and less wear-resistant than the amorphous component, theamorphous component being more ductile and more wear-resistant.

[0030] In the present invention, the degree of crystallinity of thepolymer is preferably reduced by crosslinking. The crosslinking can beachieved by various methods known in the art, for example, byirradiation crosslinking of the molten polymer; photocrosslinking of themolten polymer; and crosslinking of the polymer with a free radicalgenerating chemical. The preferred method is chemical crosslinking. Asindicated, if the crosslinking is to be achieved by irradiation, thepolymer should be irradiated in the melt, unlike the above mentionedprior art irradiation methods, such as in Oonishi et al. Applicants alsodiscovered that such a crosslinked polymer is useful for in vivo implantbecause it is wear resistant. Such in vivo implant has not beenenvisioned by the prior art. Moreover, since acetabular cups areroutinely sterilized by irradiation which increases the crystallinity ofUHMW polyethylene (Bhateja, S. K., J. Macromol. Sci. Phys., B22:159(1983); Bhateja, S. K., et al., J. Polym. Sci., Polym. Phys. Ed., 21:523(1983); and Bhateja, S. K. & Andrews, E. H., J. Mater. Sci., 20:2839(1985)), applicants realized that the irradiation in fact makes thepolymer more susceptible to wear, contrary to the teaching of the priorart such as Oonishi et al, supra. By crosslinking the polymer beforesterilization by irradiation, applicants' method mitigates thedeleterious effects of irradiation, such as chain scission. Applicants'method calls for determination of the crystallinity after irradiation toadjust the crosslinking conditions to reduce crystallinity. The polymermay also be irradiated under certain conditions e.g., in nitrogenatmosphere to reduce the immediate and subsequent amounts of oxidation.Reducing oxidation increases the amount of crosslinking. In producingacetabular cups, applicants discovered that both uncrosslinked andcrosslinked cups show shrinkage in size, but crosslinked cups tend toshrink more than uncrosslinked cups. Thus, the present invention alsoprovides for annealing the crosslinked polymer in order to shrink it toa stable size before reshaping the polymer.

[0031] Most importantly, implants which are produced by the foregoingmethods of the invention are more wear resistant than conventionaluntreated polymer. Thus, an example of the present invention presents anUHMW polyethylene acetabular cup of a total hip prosthesis which hasbeen chemically crosslinked by a peroxide, and then sterilized byirradiation, showing only one fifth of the wear of a control cup after asimulated year of in vivo use.

Method for Treating the Polymers

[0032] One aspect of the invention presents a method for treating apolymer to reduce its crystallinity to less than 45% to enable theresulting polymer to better withstand wear. The polymer's crystallinityis preferably reduced by crosslinking in the molten state followed bycooling to the solid state. Preferably, the crosslinking reduces thecrystallinity of the polymer by about 10% to 50%; more preferably, byabout 10% to 40%; and most preferably, by about 10% to 30% compared toan uncrosslinked polymer. For example, the preferable degree ofcrystallinity of crosslinked UHMW polyethylene is between about 24% to44%; more preferably, between 29% to 44%; and most preferably, betweenabout 34% to 44% After sterilization by irradiation, the crosslinkedpolymer has a reduced crystallinity compared to the uncrosslinkedpolymer. Preferably, the irradiated crosslinked polymer possesses about10% to 50%; more preferably, about 10% to 40%; and most preferably,about 10% to 30% less. degree of crystallinity compared to theuncrosslinked but irradiated polymer. For example, the preferable degreeof crystallinity of irradiated, crosslinked UHMW polyethylene is betweenabout 28% to 51%; more preferably, between about 33% to 51%; and mostpreferably, between about 39% to 51%. For example, EXAMPLE 1, Table 1below shows the degree of crystallinity for UHMW polyethylene containingdifferent weight percentage of peroxide. In the following EXAMPLE 2,UHMW polyethylene which was crosslinked by 1% weight (wt) peroxideexhibited about 39.8% crystallinity, i.e. about a 19% reduction incrystallinity compared to uncrosslinked UHMW polyethylene whichpossessed about 49.2% crystallinity. After gamma irradiation to anaverage dose of about 3.4 Mrad, the crosslinked UHM polyethylene,exhibits about 42% crystallinity, i.e., a reduction of about 25% incrystallinity compared to the originally uncrosslinked but radiationsterilized UHMW polyethylene which possessed about 55.8% crystallinity.Thus, it is contemplated that after the usual sterilization dosage inthe solid state, which generally averages between 2.5 to 4.0 Mrad, thetreated polymer preferably possesses less than about 45% crystallinity,and more preferably about 42% crystallinity or less. Also, the treatedpolymer preferably possesses less than about 43%, more preferably lessthan about 40%, crystallinity before irradiation in the solid state.

[0033] If the polymer is to be molded, e.g. as an acetabular cup, thepolymer may be placed in the mold and crosslinked therein. Furthercrosslinking examples are: (1) irradiation of the polymer when it is ina molten state, e.g. UHMW polyethylene has been crosslinked in the meltby electron beam irradiation; and molten linear polyethylene has beenirradiated with fast electrons (Dijkstra, D. J. et al., Polymer,30:866-709 (1989); Gielenz G. & Jungnickle, B. J., Colloid & PolymerSci., 260:742-753 (1982)); the polymer may also be gamma-irradiated inthe melt; and (2) photocrosslinking of the polymer in the melt, e.g.polyethylene and low-density polyethylene have been photocrosslinked(Chen, Y. L. & Ranby, B., J. Polymer Sci.: Part A: Polymer Chemistry,27:4051-4075, 4077-4086 (1989)); Qu, B. J. & Ranby, B., J. AppliedPolymer Sci. 48:71i-719 (1993)).

Choices of Polymers

[0034] The polymers are generally polyhydrocarbons. Ductile polymersthat wear well are preferred. Examples of such polymers include:polyethylene, polypropylene, polyester and polycarbonates. For example,UHMW polymers may be used, such as UHMW polyethylene and UHMWpolypropylene. An UHMW polymer is a polymer having a molecular weight(MW) of at least about a million.

[0035] For in vivo implants, the preferred polymers are those that arewear resistant and have exceptional chemical resistance. UHMWpolyethylene is the most preferred polymer as it is known for theseproperties and is currently widely used to make acetabular cups fortotal hip prostheses. Examples of UHMW polyethylene are: Hostalen GUR415 medical grade UHMW polyethylene flake (Hoechst-Celanese Corporation,League City, Tex.), with a weight average molecular weight of 6×10⁶ MW;Hostalen GUR 412 with a weight average molecular weight of between2.5×10⁶ to 3×10 MW; Hostalen GUR 413 of 3×10 to 4×10 MW; RCH 1000(Hoechst-Celanese Corp.); and HiFax 1900 of 4×10⁶ MW (HiMont, Elkton,Md.). GUR 412, 413 and 415 are in the form of powder. RCH 1000 isusually available as compression molded bars. Historically, companieswhich make implants have used GUR 412 and GUR 415 for making acetabularcups. Recently, Hoechst-Celanese Corp. changed the designation of GUR415 to 4150 resin and indicated that 4150 HP was for use in medicalimplants.

Methods for Characterizing the Polymers (Especially the Determination ofTheir Crystallinity

[0036] The degree of crystallinity of the crosslinked polymer may bedetermined after it has been crosslinked or molded. In case the treatedpolymer is further irradiated, e.g., to sterilize the polymer before itsimplant into humans, the degree of crystallinity may be determined afterirradiation, since irradiation effects further crystallization of thepolymer.

[0037] The degree of crystallinity can be determined using methods knownin the art, e.g. by differential scanning calorimetry (DSC), which isgenerally used to assess the crystallinity and melting behavior of apolymer. Wang, X. & Salovey, R., J. App. Polymer Sci., 34: 593-599(1987).

[0038] X-ray scattering from the resulting polymer can also be used tofurther confirm the degree of crystallinity of the polymer, e.g. asdescribed in Spruiell, J. E., & Clark, E. S.,in “Methods of ExperimentalPhysics”, L. Marton & C. Marton, Eds., Vol. 16, Part B, Academic Press,New York (1980).; Swelling is generally used to characterize crosslinkdistributions in polymers, the procedure is described in Ding, Z. Y., etal., J. Polymer Sci.. Polymer Chem., 29: 1035-38 (1990). Another methodfor determining the degree of crystallinity of the resulting polymer mayinclude FTIR {Painter, P. C. et al., “The Theory of VibrationalSpectroscopy And Its Application To Polymeric Materials”, John Wiley andSons, New York, U.S.A. (1982)} and electron diffraction. FTIR assessesthe depth profiles of oxidation as well as other chemical changes suchas unsaturation (Nagy, E. V., & Li, S., “A Fourier transform infraredtechnique for the evaluation of polyethylene orthopaedic bearingmaterials”, Trans. Soc. for Biomaterials, 13:109 (1990); Shinde, A. &Salovey, R., J. Polymer Sci., Polym. Phys. Ed., 23:1681-1689 (1985)). Afurther method for determining the degree of crystallinity of theresulting polymer may include density measurement according to ASTMD1505-68.

Methods for Chemically Crosslinking the Polymers

[0039] The polymer is preferably chemically crosslinked to decrease itscrystallinity. Preferably, the crosslinking chemical, i.e. a freeradical generating chemical, has a long half-life at the moldingtemperature of the chosen polymer. The molding temperature is thetemperature at which the polymer is molded. The molding temperature isgenerally at or above the melting temperature of polymer. If thecrosslinking chemical has a long half-life at the molding temperature,it will decompose slowly, and the resulting free radicals can diffuse inthe polymer to form a homogeneous crosslinked network at the moldingtemperature. Thus, the molding temperature is also preferably highenough to allow the flow of the polymer to occur to distribute ordiffuse the crosslinking chemical and the resulting free radicals toform the homogeneous network. For UHMW polyethylene, the moldingtemperature is between 150° to 220° C. and the molding time is between 1to 3 hours; the preferable molding temperature and time being 170° C.and 2 hours, respectively.

[0040] Thus, the crosslinking chemical may be any chemical thatdecomposes at the molding temperature to form highly reactiveintermediates, free radicals, which would react with the polymers toform the crosslinked network. Examples of free radical generatingchemicals are peroxides, peresters, azo compounds, disulfides,dimethacrylates, tetrazenes, and divinyl benzene. Examples of azocompounds are: azobis-isobutyronitride, azobis-isobutyronitrile, anddimethylazodi isobutyrate. Examples of peresters are t-butyl peracetateand t-butyl perbenzoate.

[0041] Preferably the polymer is crosslinked by treating it with anorganic peroxide. The preferable peroxides are2,5-dimethyl-2,5-bis(tert-butylperoxy)-3-hexyne (Lupersol 130, AtochemInc., Philadelphia, Pa.); 2,5-dimethyl-2,5-di-(t-butylperoxy)-hexane;t-butyl α-cumyl peroxide; di-butyl peroxide; t-butyl hydroperoxide;benzoyl peroxide; dichlorobenzoyl peroxide; dicumyl peroxide;di-tertiary butyl peroxide; 2,5 dimethyl-2,5 di(peroxy benzoate)hexyne-3; 1,3-bis(t-butyl peroxy isopropyl) benzene; lauroyl peroxide;di-t-amyl peroxide; 1,1-di-(t-butylperoxy)cyclohexane;2,2-di-(t-butylperoxy)butane; and 2,2-di-(t-amylperoxy) propane. Themore preferred peroxide is2,5-dimethyl-2,5-bis(tert-butylperoxy)-3-hexyne. The preferred peroxideshave a half-life of between 2 minutes to 1 hour; and more preferably,the half-life is between 5 minutes to 50 minutes at the moldingtemperature.

[0042] Generally, between 0.2 to 5.0 wt % of peroxide is used; morepreferably, the range is between 0.5 to 3.0 wt % of peroxide; and mostpreferably, the range is between 0.6 to 2 wt %.

[0043] The peroxide can be dissolved in an inert solvent before beingadded to the polymer powder. The inert solvent preferably evaporatesbefore the polymer is molded. Examples of such inert solvents arealcohol and acetone.

[0044] For convenience, the reaction between the polymer and thecrosslinking chemical, such as peroxide, can generally be carried out atmolding pressures. Generally, the reactants are incubated at moldingtemperature, between 1 to 3 hours, and more preferably, for about 2hours.

[0045] The reaction mixture is preferably slowly heated to achieve themolding temperature. After the incubation period, the crosslinkedpolymer is preferably slowly cooled down to room temperature. Forexample, the polymer may be left at room temperature and allowed to coolon its own. Slow cooling allows the formation of a stable crystallinestructure.

[0046] The reaction parameters for crosslinking polymers with peroxide,and the choices of peroxides, can be determined by one skilled in theart. For example, a wide variety of peroxides are available for reactionwith polyolefins, and investigations of their relative efficiencies havebeen reported (Lem, K. W. & Han, C. D., J. Appl. Polym. Sci., 27:1367(1982); Kampouris, E. M. & Andreopoulos, A. G., J. Appl. Polym. Sci.,34:1209 (1987) and Bremner, T. & Rudin, A. J. Appl. Polym. Sci., 49:785(1993)). Differences in decomposition rates are perhaps the main factorin selecting a particular peroxide for an intended application (Bremner,T. & Rudin, A. J. Appl. Polym. Sci., 49:785 (1993)). Bremner and Rudin,id., compared three dialkyl peroxides on the basis of their ability toincrease the gel content, crosslinking efficiency, and storage modulusof virgin polyethylene through a crosslinking mechanism and found thatthey decreased in the order of α,α-bis(tertiarybutylperoxy)-p-diisopropyl benzene >dicumylperoxide >2,5-dimethyl-2,5-di-(tertiary butylproxy)-hexyne-3 at the sameactive peroxide radical concentrations and temperature.

[0047] More specifically, peroxide crosslinking of UHMW polyethylene hasalso been reported (de Boer, J. & Pennings, A. J., Makromol. Chem. RapidCommun, 2:749 (1981); de Boer, J. & Pennings, A. J., Polymer, 23:1944(1982); de Boer, J., et al., Polymer, 25:513 (1984) and Narkis, M., etal., J. Macromol. Sci. Phys., B 26:37, 58 (1987)). de Boer et al.crosslinked UHMW polyethylene in the melt at 180° C. by means of2,5-dimethyl-2,5-di-(tert-butylperoxy)-hexyne-3 and found thatcrosslinks and entanglements, whether trapped or not, contributed to thesame degree to the decrease in crystallinity of UHMW polyethylene uponcrosslinking (de Boer, J. & Pennings, A. J., Polymer, 23:1944 (1982)).It was concluded that an almost completely crosslinked (or gelled)material with high crystallinity and good mechanical properties could beobtained by using as little as 0.2-0.3 wt % of peroxide.

[0048] Some of the above references investigated the effect of peroxidecrosslinking on UHMW polyethylene, such as in lowering crystallinity;and the effects of reaction parameters, such as peroxide concentrations(de Boer, J. & Pennings, A. J., Polymer, 23:1944 (1982); Narkis, M., etal., J. Macromol. Sci. Phys., B 26:37-58 (1987)). However, thesereferences do not address the effect of peroxide crosslinking or thelowering of crystallinity in relation to the wear property of theresulting polymer. For example, de Boer and Pennings, in Polymer,23:1944 (1982), were concerned with the effect of crosslinking on thecrystallization behavior and the tensile properties of UHMWpolyethylene. The authors found that tensile properties, such as tensilestrength at break point and Young's modulus, of the UHMW polyethylene,showed a tendency to decrease with increasing peroxide content.

[0049] Similarly, Narkis, M., et al., J. Macromol. Sci. Phys., B26:37-58 (1987), separately determined the effects of irradiation andperoxide on the crosslinking and degree of crystallinity of UHMWpolyethylene (Hostalen GUR 412),. high molecular weight polyethylene,and normal molecular weight polyethylene. However, M. Narkis et al., didnot study the inter-relationship of peroxide crosslinking andirradiation, nor their effects on wear resistance.

Use of Crosslinked Polymers for In Vivo Implants

[0050] Another aspect of the invention presents a process for making invivo implants using the above chemically crosslinked polymer. Since invivo implants are often irradiated to sterilize them before implant, thepresent invention provides the further step of selecting for implantuse, a polymer with about 45% crystallinity or less after irradiationsterilization. For γ-irradiation sterilization, the minimum dosage isgenerally 2.5 Mrad. The sterilization dosage generally falls between 2.5and 4.0 Mrad. The preferable degree of crystallinity is between 25% to45% crystallinity. In EXAMPLE 2 below, the polymer has about 39.8%crystallinity after crosslinking; and about 42% crystallinity afterfurther irradiation with γ-radiation to an average dose of about 3.4Mrad. Thus, the chemically crosslinked UHMW polymer preferably possessesless than about 43% crystallinity before irradiation in the solid state,and less than about 45% crystallinity after irradiation with γ-radiationto an average dose of about 3.4 Mrad.

Annealing of Crosslinked Polymers

[0051] Applicants observed that both crosslinked and uncrosslinkedpolymers tended to shrink, but the crosslinked polymer tended to shrinkmore than the uncrosslinked polymer (see EXAMPLE 3 below). Thus, thepresent invention further provides for annealing a polymer to pre-shrinkit to a size which will not shrink further (i.e. stabilize the polymer'sshrinkage or size). Thus, one aspect of the invention provides for amethod of: 1) crosslinking a polymer, 2) selecting a crosslinked polymerof reduced crystallinity, 3) annealing the polymer to stabilize itssize. Thus, the polymer can be molded at a size larger than desired, andthe molded polymer is then annealed to stabilize its size. After sizestabilization, the molded polymer is then resized, such as by machining,into a product with the desired dimension.

[0052] The annealing temperature is preferably chosen to avoid thermaloxidation of the crosslinked polymer which will increase itscrystallinity. Thus, the annealing temperature is preferably below themelting point of the molded polymer before irradiation. For example, themelting temperatures of molded UHMW polyethylene and molded 1 wt %peroxide UHMW polyethylene are 132.6° C. and 122.3° C., beforeirradiation, respectively. The preferable annealing temperature for boththese molded UHMW polyethylenes is between 60° C. to 120° C., beforeirradiation, and more preferably 100° C. These temperatures weredetermined by observation, based on experiments, of their minimal effecton thermal oxidation of the molded polymers. The annealing time isgenerally between 1 to 6 hours, and more preferably between 2 to 4hours. In the case of UHMW polyethylene, the annealing time ispreferably between 2 to 4 hours, and more preferably about 2 hours.

[0053] To further avoid thermal oxidation of the crosslinked polymer,the annealing is most preferably conducted in a vacuum oven.

[0054] To ensure that the crosslinked and annealed polymer has thedesired degree of crystallinity, its degree of crystallinity ispreferably determined after the annealing process, using the method(s)described previously.

Wear-Resistant Polymers

[0055] Another aspect of the invention presents a polymer with 45% ofcrystallinity or less, in particular, after irradiation in the solidstate and/or annealing. In EXAMPLE 2 below, the polymer has about 39.8%crystallinity after crosslinking; and about 42% crystallinity, afterfurther irradiation with γ-radiation to an average dose of about 3.4Mrad; or about 40.8% crystallinity, after crosslinking and annealing,but before irradiation in the solid state.

[0056] The polymers of the present invention cat be used in anysituation where a polymer, especially p polyethylene, is called for, butespecially in situations where high wear resistance is desired andirradiation of the solid polymer is called for. More particularly, thesepolymers are useful for making in vivo implants.

In Vivo Implants Made of Crosslinked Polymers

[0057] An important aspect of this invention presents in vivo implantsthat are made with the above polymers or according to the methodpresented herein. These implants are more wear resistant than theiruntreated counterpart, especially after irradiation. In particular,these in vivo implants are chemically crosslinked UHMW polymers, whichhave been molded, annealed, and resized into the shape of the implants.Further, the chemically crosslinked UHMW polymer preferably possessesless than about 43% crystallinity before irradiation in the solid state,and less than about 45% crystallinity, after γ-irradiation to an averagedose of 3.4 Mrad, in the solid state. The modified polymer can be usedto make in vivo implants for various parts of the body, such ascomponents of a joint in the body. For example, in the hip joints, themodified polymer can be used to make the acetabular cup, or the insertor liner of the cup, or trunnion bearings (e.g. between the modular headand the stem). In the knee joint, the modified polymer can be used tomake the tibial plateau (femoro-tibial articulation), the patellarbutton (patello-femoral articulation), and trunnion or other bearingcomponents, depending on the design of the artificial knee joint. In theankle joint, the modified polymer can be used to make the talar surface(tibio-talar articulation) and other bearing components. In the elbowjoint, the modified polymer can be used to make the radio-humeral joint,ulno-humeral joint, and other bearing components. In the shoulder joint,the modified polymer can be used to make the glenoro-humeralarticulation, and other bearing components. In the spine, the modifiedpolymer can be used to make intervertebral disk replacement and facetjoint replacement. The modified polymer can also be made intotemporo-mandibular joint (jaw) and finger joints. The above are by wayof example, and are not meant to be limiting.

[0058] Having described what the applicants believe their invention tobe, the following examples are presented to illustrate the invention,and are not to be construed as limiting the scope of the invention.

EXAMPLES Example 1 Experimental Details

[0059] Commercial-grade UHMW polyethylene GUR 415 (from Hoechst-CelaneseCorporation, League City, Tex.), with a weight average molecular weightof 6×106, was used as received. The peroxide used was2,5-dimethyl-2,5-bis(tert-butylperoxy)-3-hexyne (Lupersol 130, AtochemInc., Philadelphia, Pennsylvania). The reason for choosing Lupersol 130was its long half-life at,elevated temperature. The peroxide willdecompose slowly, and the resultant free radicals can diffuse in thespecimen to form a homogeneous network at elevated temperatures.

[0060] Mixing of the UHMW polyethylene and the peroxide was accomplishedby dispersing polyethylene powder in an acetone solution of the peroxideand subsequently evaporating the solvent (de Boer, J., et al., J. Polym.Sci., Polym. Phys. Ed., 14:187 (1976); de Boer, J. & Pennings, A. J.,Makromol. Chem, Rapid Commun., 2:749 (1981) and de Boer, J. & Pennings,A. J., Polymer, 23:1944 (1982)). The mixed powder (22g) was poured intothe mold cavity and then compression molded in a mold between twostainless-steel plates at 120° C. and ram pressure 11×103 kPa for 10minutes in order to evacuate the trapped air in the powder. Afterpressing, the pressure was reduced to 7.5×10³ kPa and the specimen washeated to 170° C. by circulated heating oil. These conditions were heldfor 2 hours. The half-life time of peroxide at 170° C. in dodecane isabout 9 minutes. After 2 hours, pressure was increased to 15×10³ kPa toavoid cavities in the specimen and sink marks on the surface and thespecimen was slowly cooled in the mold to room temperature. The mold wasin the shape of an acetabular cup for a total hip prosthesis.

[0061] The specimens were irradiated with γ-rays at room temperature inair atmosphere by SteriGenics International (Tustin, Calif.). Cobalt-60was used as a source of gamma irradiation. The radiation doses weredelivered at a dose rate of 5 kGy/hr. Specimens received doses to anaverage of about 34 kGy (i.e., an average of about 3.4 Mrad).

[0062] The physical properties of specimens before and after irradiationwere characterized by DSC, equilibrium swelling, FTIR, and WAXSmeasurements. Surface morphology was examined by SEM.

Results and Discussion

[0063] Before irradiation, the degree of crystallinity, peak meltingtemperature, and recrystallization temperature for the peroxide-freespecimen are 49.2%, 132.6 and 115.5° C., respectively. For a 1 wt %peroxide specimen, the degree of crystallinity, peak meltingtemperature, and recrystallization temperature are reduced to 39.8%,122.3 and 110.1° C., respectively. Peroxide crosslinking reactions areaccompanied by the decomposition of peroxide and abstraction of hydrogenatoms, and the resulting combination of alkyl radicals to producecarbon-carbon crosslinks. Generally, this reaction was performed abovethe melting temperature of the polymer. Thus the crosslinking steppreceded the crystallization step. It was suggested that crystallizationfrom a crosslinked melt produced an imperfect crystal, and crosslinkssuppressed crystal growth, resulting in the depression of meltingtemperature and a decreased crystallinity (decreased crystallite size)(de Boer, J. et al., J. Polym. Sci., Polym. Phys. Ed., 14:187 (1976); deBoer, J. & Pennings, A. J., Makromol. Chem, Rapid Commun., 2:749 (1981);de Boer, J. & Pennings, A. J., Polymer, 23:1944 (1982) and Narkis, M.,et al., J. Macromol. Sci. Phys., B26:37 (1987)). Wide-angle x-rayscattering shows that the degree of crystallinity, crystal perfectionand size decrease after peroxide crosslinking. For swelling measurement,the peroxide-free specimen dissolves completely in boiling p-xylene. Thegel content, degree of swelling, and average molecular weight betweencrosslinks for the 1 wt % peroxide specimen are 99.6%, 2.53, and 1322(g/mol), respectively. Because of the extremely long polymer chains inUHMW polyethylene, only a few crosslinks were needed for gelation. Inaddition, an almost 100% gel can be obtained by peroxide crosslinkingbecause no chain scission occurs by peroxide crosslinking.

[0064] After irradiation, the degree of crystallinity and peak meltingtemperature for the peroxide-free specimen were increased to 55.8% and135° C., respectively. It was suggested that irradiation-inducedscission of taut tie molecules permits recrystallization of brokenchains from the noncrystalline regions, and results in an increase inthe degree of crystallinity and an increased perfection of existingfolded chain crystallites (Narkis, M., et al., J. Macromol. Sci. Phys.,B26:37 (1987); Bhateja, S. K., J. Macromol. Sci. Phys., B22:159 (1983);Bhateja, S. K., et al., J. Polym. Sci., Polym. Phys. Ed., 21:523 (1983);Kamel, I. & Finegold, L., J. Polym. Sci., Polym. Phys. Ed., 23:2407(1985); Shinde, A. & Salovey, R., J. Polym. Sci., Polym. Phys. Ed.,23:1681 (1985); Bhateja, S. K. & Andrews, E. H., J. Mater. Sci., 20:2839(1985); Minkova, L., Colloid Polym. Sci., 266:6 (1988); Minkova, L. &Mihailov, M., Colloid Polym. Sci., 268:1018 (1990) and Zhao, Y., et al.,J. Appl. Polym. Sci., 50:1797 (1993)). The gel content after irradiationfor the peroxide-free specimen was 70.8%.

[0065] For the 1 wt % peroxide specimen, the degree of crystallinity andpeak melting temperature after irradiation were increased to 42% (about2% increase) and 125.1° C., respectively. The gel content decreased to97.5% after irradiation, whereas, the degree of swelling and molecularweight between crosslinks increased to 3.35 and 2782 (g/mol),respectively. Apparently, irradiation-induced scission of taut tiemolecules resulted in a decreased gel content and an increased degree ofswelling. However, after peroxide crosslinking, the effect ofirradiation on network properties was mitigated. As a result of peroxidecrosslinking, radiation-induced chain scission becomes less important indetermining gel content. We suggest that peroxide crosslinking reducesthe effect of irradiation on the crosslinked network because crosslinksintroduced by peroxide crosslinking stabilize chain fragments resultingfrom the scission of taut tie molecules and suppress recrystallizationof broken chains. Wide-angle x-ray scattering showed that crystalperfection increased after irradiation. It is suggested that crystalperfection was improved by irradiation-induced scission of taut tiemolecules in the amorphous regions.

[0066] FTIR measurements showed that, after irradiation, the carbonylconcentration significantly increased. This is because the free radicalsproduced by irradiation reacted with oxygen dissolved and/or diffused inthe polymer. In addition, the carbonyl concentration in irradiatedperoxide-crosslinked samples was higher, compared to the peroxide-freesample (after irradiation). Peroxide crosslinking produces tertiarycarbons, therefore, the concentration of tertiary carbons increases withincreasing peroxide concentration. Applicants believe that tertiarycarbons are more susceptible to oxidation during irradiation. Therefore,carbonyl concentration in the irradiated peroxide-crosslinked samplesincreased with increasing peroxide concentration.

[0067] After irradiation, scanning electron micrographs were taken ofthe fracture surfaces of the peroxide-free and 1 wt % peroxidespecimens, compression molded at 170° C. for 2 hours and subsequentlyslowly cooled to room temperature. The micrographs are shown in FIGS. 1and 2, respectively. As shown in FIG. 1, a brittle (rough) fractureboundary of size comparable to that of the original UHMW polyethylenepowder particles is observed. Close examination (×5000 magnification)shows an oriented nodular structure, composed of many smooth, submicronspheres. These smooth, minute spheres are believed to correspond tothose present in the raw UHMW polyethylene powder and to form anaggregate. In FIG. 2, peroxide crosslinked samples show a ductile(smooth) fracture surface, compared to the rough fracture surface ofperoxide-free specimen. The difference in appearance of fracturesurfaces for peroxide-free and 1 wt % peroxide specimens is due to thecrystallinity difference. After irradiation, the degree of crystallinityfor the peroxide-free and 1 wt % peroxide specimens were 55.8 and 42%,respectively. It is believed that the peroxide-free specimen (55.8%crystallinity) suffered higher forces and less deformation duringfracturing process, leading to a sharp break in the polymer.

[0068] The crosslinking experiment was also conducted with differentconcentrations of Lupersol 130, using a smaller amount, 5 g, of GUR 415and a smaller mold which was in the form of a disk. It was observed thatthe degree of crystallinity of the crosslinked polymer decreased withincreased concentrations of Lupersol 130. The result is shown in Table 1below: TABLE 1 wt % Crystallinity (%) Crystallinity (%) Peroxide BeforeIrradiation After Irradiation 0 49.2 55.8 0.2 44.0 50.0 0.4 41.6 46.80.6 41.3 46.2 0.8 40.0 45.0 1.0 39.8 42.0 1.5 36.8 36.8 2.0 36.5 36.7

Conclusions

[0069] Peroxide crosslinking leads to a decrease in the degree ofcrystallinity, peak melting temperatures, and recrystallizationtemperatures for 1 wt % peroxide specimen. Irradiation producescrosslinking in amorphous regions plus extensive scission of taut tiemolecules and leads to increased crystallinity and crystal perfection,reduces gel content, and increases the degree of swelling of acrosslinked network.

[0070] Peroxide crosslinking reduces the effect of irradiation on thecrosslinked network. This is because crosslinks introduced by peroxidecrosslinking can stabilize the chain fragments resulting from thescission of taut tie molecules and suppress recrystallization of brokenchains.

[0071] FTIR measurements showed that, after irradiation, the carbonylconcentration significantly increased. This is because the free radicalsproduced by irradiation react with oxygen dissolved and/or diffused inthe polymer. In addition, carbonyl concentration in the irradiatedperoxide-crosslinked samples is higher, compared to the peroxide-freesample (after irradiation). This is because peroxide crosslinkingintroduces tertiary carbons which are more susceptible to oxidationduring irradiation, so that the carbonyl concentration in the irradiatedperoxide-crosslinked samples increases.

[0072] Wide-angle x-ray scattering shows that crystal perfectionincreases after irradiation. It is suggested that crystal perfection isimproved by irradiation-induced scission of taut tie molecules in theamorphous regions.

[0073] The peroxide-free specimen shows brittle fracture because ofhigher crystallinity (55.8%), whereas, the 1 wt % peroxide specimenshows ductile fracture due to lower crystallinity (42%).

Example 2 Materials and Methods

[0074] In this example, the wear resistance of the polyethylenes treated(modified) and untreated (unmodified) with peroxide in EXAMPLE 2 weretested. The control (unmodified) and modified polyethylenes werecompression molded directly into the form of acetabular cups. These werethen exposed to an average of approximately 3.4 Mrad of gamma radiation(SteriGenics International, Tustin, Calif.), to simulate the conditionof cups that would be used in patients. Due to different amounts ofpost-molding shrinkage, the internal surface of each cup was machined toprovide nearly identical internal diameters and ball-to-cup clearancesamong the control and modified cups (FIG. 3). As shown in FIG. 3B, thecup's outer radius 1 is 24.5 mm, its inner radius 2 is 16.1 mm, itsheight 3 is 29.8 mm, and its diameter 4 is 49.0 mm The cups werepre-soaked in distilled water for three weeks prior to the wear test tominimize fluid absorption during the wear test. The wear cups weremounted on the hip joint simulator, including four cups of controlpolyethylene and three cups of modified polyethylene. Each cup was heldin a urethane mold and mounted in a stainless steel test chamber, with aplexiglass wall to contain the bovine serum lubricant. The lubricant had0.2% sodium azide added to retard bacterial degradation, and 20milli-Molar ethylene-diaminetetraacetic acid (EDTA) to preventprecipitation of calcium phosphate on the surfaces of the ball(McKellop, H. & Lu, B., “Friction and Wear of Polyethylene-Metal andPolyethylene-Ceramic Hip Prostheses on a Joint Simulator, Fourth WorldBiomaterials Congress, Berlin, Apr. 1992, 118). A polyethylene skirtcovered each chamber to minimize air-borne contamination. The cups wereoscillated against highly polished femoral balls of cast cobalt-chromiumalloy, as used on artificial hips. The simulator applied a Paul-typecyclic load at one cycle per second (Paul, J. P., Proc. Instn. Mech.Enqrs., 181, Part 3J, 8-15, (1967)) with a 2000N peak, simulating theload on the human hip during normal walking, and the cups wereoscillated through a bi-axial 46 degree arc at 68 cycles per minute. Atintervals of 250,000 cycles, the cups were removed from the wearmachine, rinsed, inspected and replaced with fresh lubricant. At 500,000cycles and one million cycles, all of the cups were removed from thewear simulator, cleaned, dried and weighed to determine the weight lossdue to wear. One million cycles is the equivalent of about one year'suse of a prosthetic hip in a patient. FIG. 4 presents a schematicdiagram of the hip joint simulator. The arrow indicates the direction ofthe computer controlled simulated physiological load exerted on thesimulated hip joint. The simulator contains: a torque transducer 5, theacetabular cup 6, a dual axis offset drive block 7, a test chamber 8,serum 9, and a femoral head 10.

[0075] Three soak-correction acetabular cups of each material (controland modified) were prepared in an identical manner, but were not weartested. These cups were mounted in a separate test frame and a cyclicload, identical to that used in the wear test, was applied. Thesesoak-correction cups were cleaned and weighed together with the weartest cups, and the average weight gain of the correction cups was addedto the apparent weight loss of the wear test cups (i.e. to correct forfluid absorption by the wear test cups that would obscure the weightloss due to wear).

Results and Discussion

[0076] Because of the apparent “negative” wear at 0.5 million cycles(discussed below), the wear rates were calculated and compared for allof the cups only for the interval from 0.5 to 1.0 million cycles. Thefour control polyethylene cups showed comparable amounts of wear (FIG.4), with an average corrected wear rate of 19.19 (S.D.=2.38) milligramsper million cycles (Table 2). This was within the range that applicantshave measured for cups of conventional UHMW polyethylene in a variety ofstudies that applicants have run.

[0077] The wear was much lower for the modified cups (FIG. 5). As shownin Table 2, the mean wear rate for the modified cups was 4.12(S.D.=1.26) milligrams per million cycles, i.e. about one-fifth of thewear of the control cups. This difference was statistically significantat the level of p=0.0002). TABLE 2 WEAR RATES FOR CONTROL AND MODIFIEDPOLYETHYLENES (INTERVAL FROM 0.5 TO 1.0 MILLION CYCLES) MEAN WEAR RATECUP WEAR RATE (STANDARD MATERIAL NUMBER (mg/million cycles) DEVIATION)CONTROL C2 21.67 19.19 POLYETHYLENE C3 16.78 (2.38) C4 17.57 C9 20.76MODIFIED M4 4.08  4.12 POLYETHYLENE M5 2.88 (1.26) M7 5.39

[0078] For the data point at 0.5 million cycles, the corrected weightswere lower than the weights before the wear test. This was most likelythe result of the wear being very small, and the fluid absorption by thetest cups being slightly greater than the average gain of the soakcorrection cups, such that the correction factor did not entirely offsetthe fluid gain by the wear cups (giving an apparent “negative” wear). Asmall difference in water absorption rates between the wear cups and thecorrection cups could arise due to differences in equilibriumtemperatures (the wear cups were typically at 35° C. to 45° C., whereasthe soak correction cups were at room temperature, about 20° C.), due tomechanical agitation of the serum during oscillation of the wear testchambers, or other causes.

Example 3

[0079] During the wear test in the simulator described in EXAMPLE 2, itwas discovered that the acetabular cups shrunk at simulated human bodytemperature. In order to stabilize the shrinkage, in this experiment(unrelated to EXAMPLE 2), the cups were annealed at 100° C. in a vacuumoven for 2 hours. After annealing, the total shrinkage in diameter foruncrosslinked and crosslinked cups was approximately 1% and 2%,respectively. The degrees of crystallinity of the annealed cups weredetermined by DSC. The degree of crystallinity of the uncrosslinkedpolymer -was unchanged, whereas that of the crosslinked polymer wasincreased by approximately 1%. To test for further shrinkage, the cupswere again put in the vacuum oven at 80° C. for two hours, and nofurther shrinkage was observed.

[0080] The present invention has been described with reference tospecific embodiments. However, this application is intended to coverthose changes and substitutions which may be made by those skilled inthe art without departing from the spirit and scope of the appendedclaims.

We claim:
 1. A method for producing a crosslinked polymer with increased ability to withstand wear, comprising the steps of: a) crosslinking a polymer to form a crosslinked polymer; b) determining the degree of crystallinity of the crosslinked polymer; and c) adjusting reaction conditions such that the degree of crystallinity of the polymer after crosslinking is reduced by 10% to 50%;  wherein the crosslinking is achieved by a method selected from the group consisting of: i) irradiation crosslinking of the polymer when it is in a molten state; ii) photocrosslinking of the polymer in the melt; and iii) crosslinking of the polymer with a free radical generating chemical.
 2. The method of claim 1, further comprising the step of irradiating the crosslinked polymer in the solid state.
 3. The method of claim 2, further comprising the step of annealing the crosslinked polymer.
 4. A method for producing a crosslinked polymer with increased ability to withstand wear, comprising the steps of: a) crosslinking a polymer to form a crosslinked polymer without irradiating the polymer in its solid state; b) irradiating the crosslinked polymer in its solid state at a sterilization dose; and c) selecting for the crosslinked polymer which, after the irradiation in step (b), possesses a degree of crystallinity of about 45% or less.
 5. The method of claim 4, wherein the crosslinking is achieved by a method selected from the group consisting of: a) irradiation crosslinking of the polymer when it is in a molten state; b) photocrosslinking of the polymer in the melt; and c) crosslinking of the polymer with a free radical generating chemical.
 6. The method of claim 5, further comprising the step of annealing the crosslinked polymer.
 7. A method for producing a crosslinked polymer with increased ability to withstand wear, comprising the steps of: a) crosslinking a polymer to form a crosslinked polymer without irradiating the polymer in its solid state; b) annealing the crosslinked polymer; c) irradiating the crosslinked polymer in its solid state at a sterilization dose; and d) selecting for the crosslinked polymer which, after the irradiation in step (c) and the annealing in step (b), possesses a degree of crystallinity of about 45% or less.
 8. A method for making a crosslinked polymer suitable for use in vivo implant, said crosslinked polymer has an increased ability to withstand wear, said method comprising the steps of: a) reducing crystallinity of the polymer by crosslinking the polymer; and b) molding the resulting polymer into a shape suitable for in vivo implant;  wherein the crosslinking of step (a) does not include irradiating the polymer in a solid state.
 9. The method of claim 8, wherein the crosslinking is achieved by a method selected from the group consisting of: a) irradiation of the polymer when it is in a molten state; b) photocrosslinking of the polymer in the melt; and c) crosslinking of the polymer with a free radical generating chemical.
 10. The method of claim 9, wherein the crosslinking is achieved with a free radical generating chemical.
 11. The method of claim 10, wherein the free radical generating chemical is selected from the group consisting of: peroxides, peresters, azo compounds, disulfides, dimethacrylates, tetrazenes, and divinyl benzene.
 12. The method of claim 11, further comprising the step of radiation sterilization of the in vivo implant.
 13. The method of claim 12, wherein the degree of crystallinity of the polymer is reduced by between 10 to 50% by crosslinking.
 14. The method of claim 13, further comprising the step of annealing the crosslinked polymer to stabilize its shrinkage.
 15. The method of claim 14, wherein the polymer is UHMW polyhydrocarbon.
 16. An in vivo implant made by a polymer produced by the method comprising the steps of: a) reducing the crystallinity of the polymer to enable it to better withstand wear; and b) molding the polymer into a shape suitable for in vivo implant; wherein the reduction of crystallinity in step (a) does not include irradiating the polymer in a solid state.
 17. The in vivo implant of claim 16, wherein the step (a) is achieved by crosslinking the polymer using a method selected from the group consisting of: a) irradiation crosslinking of the polymer when it is in a molten state; b) photocrosslinking of the polymer in the melt; and c) crosslinking of the polymer with a free radical generating chemical.
 18. The in vivo implant of claim 17, wherein the polymer is chemically crosslinked with a free radical generating chemical.
 19. The in vivo implant of claim 18, wherein the free radical generating chemical is selected from the group consisting of: peroxides, peresters, azo compounds, disulfides, dimethacrylates, tetrazenes, and divinyl benzene.
 20. The in vivo implant of claim 19, wherein the crosslinking reduces the crystallinity of the polymer by 10 to 50%.
 21. The in vivo implant of claim 20, wherein the polymer is a polyhydrocarbon.
 22. The in vivo implant of claim 21, wherein the polyhydrocarbon is an UHMW polyhydrocarbon.
 23. The in vivo implant of claim 17, wherein the in vivo implant is capable of possessing about 45% crystallinity or less if irradiated by gamma irradiation to an average dose of about 3.4 Mrad or less.
 24. The in vivo implant of claim 23, wherein the polymer is UHMW polyhydrocarbon.
 25. The in vivo implant of claim 24, wherein the in vivo implant increases in its degree of crystallinity by about 1% if annealed.
 26. The in vivo implant of claim 23, wherein the free radical generating chemical is selected from the group consisting of: peroxides, peresters, azo compounds, disulfides, dimethacrylates, tetrazenes, and divinyl benzene.
 27. The in vivo implant of claim 26, wherein the polymer is chemically crosslinked by a free radical generating chemical, and the polymer is UHMW polyhydrocarbon.
 28. The in vivo implant of claim 17, capable of suffering less than or equal to one-fifth of the wear suffered by another in vivo implant made from an uncrosslinked polymer.
 29. The in vivo implant of claim 28, wherein the polymer is chemically crosslinked by a free radical generating chemical, and the polymer is UHMW polyhydrocarbon.
 30. A polyhydrocarbon capable of maintaining a degree of crystallinity of about 42% or less after gamma irradiation to an average dose of about 3.4 Mrad or less.
 31. The polyhydrocarbon of claim 30, wherein the polyhydrocarbon has a crystallinity of about 39.8% or less before the gamma irradiation.
 32. The polyhydrocarbon of claim 30, wherein the polyhydrocarbon is UHMW polyhydrocarbon.
 33. A crosslinked in vivo implant comprising a component of an animal joint, said in vivo implant being capable of suffering about one-fifth or less of the wear suffered by an uncrosslinked in vivo implant, wherein the crosslinked in vivo implant and the uncrosslinked in vivo implant are made of UHMW polyethylene and have been sterilized by irradiation, and the crosslink is achieved by a method selected from the group consisting of: a) irradiation crosslinking of the UHMW polyethylene when it is in a molten state; b) photocrosslinking of the UHMW polyethylene in the melt; and c) crosslinking of the UHMW polyethylene with a free radical generating chemical.
 34. The crosslinked in vivo implant of claim 33, wherein the in vivo implant is an acetabular cup and the crosslink is achieved by crosslinking of the UHMW polyethylene with a free radical generating chemical selected from the group consisting of: peroxides, peresters, azo compounds, disulfides, dimethacrylates, tetrazenes, and divinyl benzene.
 35. The crosslinked in vivo implant of claim 34, wherein the free radical generating chemical is a peroxide.
 36. An in vivo implant made from a polyhydrocarbon having a crystallinity of about 43% or less.
 37. The in vivo implant of claim 36, capable of maintaining a crystallinity of 45% or less after irradiation with gamma irradiation at a sterilization dose.
 38. The in vivo implant of claim 37, wherein said polyhydrocarbon is UHMW polyethylene.
 39. The in vivo implant of claim 38, wherein the UHMW polyethylene is chemically crosslinked.
 40. The in vivo implant of claim 39, wherein the UHMW polyethylene has a crystallinity of about 40% before irradiation in the solid state, and a crystallinity of about 42% after gamma irradiation to an average dose of about 3.4 Mrad.
 41. The in vivo implant of claim 36, wherein the polyhydrocarbon is chemically crosslinked. 